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J. Nat. Prod. 1996, 59, 734-737
Abietane and Rearranged Abietane Diterpenes from Salvia montbretii Gu¨lac¸ ti Topcu* and Ayhan Ulubelen† TUBITAK, Marmara Research Center, Research Institute for Basic Sciences, Department of Chemistry, P.O. Box 21, 41470, Gebze, Kocaeli, Turkey, and Faculty of Pharmacy, University of Istanbul, 34452, Istanbul, Turkey Received February 1, 1996X
From the roots of Salvia montbretii six new diterpenoids were isolated in addition to eleven known compounds. The new compounds were established as salvibretol (1), 1-oxosalvibretol (4), 6-hydroxysalvinolone (5), 7-hydroxytaxodione (6), 7,7′-bistaxodione (7), and 11,11′didehydroxy-7,7′-dihydroxytaxodione (8), using 1D and 2D NMR techniques. In previous studies on the roots and aerial parts of Salvia montbretii Benth. (Lamiaceae) we have reported the isolation of the diterpenes demethylcryptojaponol, ferruginol, ferruginyl 12-methyl ether, 14-hydroxyferruginol, hypargenin F, salvinolonyl 12-methylether, and taxodione;1,2 the triterpenes R-amyrin, lupeol, monogynol A, and its 3β-cis- and trans-coumaryl esters; oleanolic and ursolic acids; the sterol sitosterol; and the flavonoids apigenin, luteolin, and cirsiliol.3 In the present study on a new collection of the roots we have obtained six new diterpenoids (1, 4-8) constituted by two abietanes (5, 6), two rearranged abietanes (1, 4), and two dimeric compounds (7, 8). The known compounds were microstegiol,4 saprorthoquinone, salvinolone,5 candidissiol,6 11-hydroxy-12-methoxy-8,11,13abietatriene,7 1-oxoaethiopinone,8 salvicanaric acid,9 limbinol, salvilimbinol,10 taxodione,11 and ferruginol.12 Results and Discussion The EIMS of the first new compound, salvibretol (1), showed a molecular ion peak at m/z 298 analyzing for C20H26O2, and HRCIMS gave a [M + 1]+ peak at m/z 299.1988, thereby verifying the molecular formula. The 13C-NMR spectrum was consistent with a diterpene structure in which the 20 carbon atoms consisted of five methyl quartets, three methylene triplets, four methine doublets, and eight quaternary singlets. One of the quarternary carbons that was hydroxylated appeared at δ 85.0, and another occurred at δ 202.9 and was attributed to an enone carbonyl. The IR spectrum of 1 supported the presence of a tertiary hydroxyl group showing a sharp peak at 3450 cm-1, a conjugated oxo group at 1700 cm-1, as well as aromaticity and unsaturation peaks at 1500, 1565, 1600, and 1620 cm-1. The 1H-NMR spectrum of 1 showed the presence of an isopropyl group, with signals at δ 1.31 and 1.35 (each 3H, d, J ) 7 Hz, H-16 and H-17) and a methine septet at δ 3.35 (1H, J ) 7 Hz, H-15). Two methyl singlets were at δ 1.15 and 1.62 for H-18 and H-19, and another methyl singlet was observed at δ 2.42 for H-20. A diagnostic signal occurred at δ 3.83 (1H, ddd, J ) 15.0, 13.0, 5.0 Hz), being typical for H-1β and indicative of a rearranged abietane diterpene similar to analogous signals from microstegiol (2) and candidissiol (3), previously isolated from Salvia microstegia4 and Salvia candidissima.6 Downfield signals for 1 were at δ 7.48 * To whom correspondence should be addressed. Phone: (262) 6412300. FAX: (262) 6412309. E-mail:
[email protected]. gov.tr. † Faculty of Pharmacy. X Abstract published in Advance ACS Abstracts, July 1, 1996.
S0163-3864(96)00222-4 CCC: $12.00
(1H, d, J ) 8.8 Hz, H-7), 7.33 (1H, s, H-14) 7.08 (1H, d, J ) 8.8 Hz, H-6), and 6.33 (1H, br s, D2O exchangeable, C-4 OH). The HETCOR NMR experiment showed direct correlations between protons and carbons for 1 (Table 1). Although it has a structural similarity to microstegiol (2), compound 1 exhibited some chemicalshift differences, especially with one of the methyl singlets resonating at δ 1.62. It was apparent that the C-4 methyl and the C-11 hydroxy groups of 2 were interchanged in 1. The possible mechanism of this rearrangement was considered from microstegiol (2) as shown in Scheme 1. In order to assign the placement of the groups unambiguously in 1, an extensive selective INEPT experiment was carried out. Irradiation of H-15 (δ 3.35) enhanced C-14 (δ 120.7), C-16 (δ 22.3), and C-12 (δ 202.9). Irradiation of Me-18 (δ 1.15) enhanced C-4 (δ 85.0) and C-19 (δ 27.4), while irradiation of Me-19 (δ
© 1996 American Chemical Society and American Society of Pharmacognosy
Abietane Diterpenes from Salvia Table 1.
1H-
and
13C-NMR
Journal of Natural Products, 1996, Vol. 59, No. 8 735
Data of Compounds 1, 4, and 5 1a
4b
position
1H
13C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
3.83 ddd, 3.02 ddd 2.20 ddd, 1.72 m 1.60 ddd, 1.20 m
26.5 t 23.0 t 33.3 t 85.0 s 132.7 s 126.7 d 125.8 d 134.1 s 129.7 s 147.3 s 41.6 s 202.9 s 134.9 s 120.7 d 27.6 d 22.3 q 22.4 q 26.3 q 27.4 q 19.1 q
7.08 d 7.48 d
7.33 s 3.35 sept 1.31 d 1.35 d 1.15 s 1.62 s 2.42 s
1H
2.19 ddd, 1.65 dt 3.04 ddd, 2.67 dt 7.11 d 7.62 d
7.41 s 3.35 sept 1.28 d 1.33 d 1.22 s 1.67 s 2.32 s
5c 13C
1H
13C
210.8 s 41.2 t 35.1 t 84.3 s 132.2 s 126.3 d 128.1 s 126.8 s 130.4 s 147.4 s 41.2 s 202.3 s 136.6 s 121.1 d 27.8 d 22.3 q 22.3 q 25.9 q 26.2 q 18.7 q
3.0 ddd, 1.50 m 2.0 m, 1.30 m 1.90 ddd, 1.68 m
36.6 t 17.9 t 30.4 t 37.6 s 170.8 s 141.0 s 180.0 s 123.2 s 132.9 s 38.3 s 143.4 s 145.6 s 138.3 s 116.6 d 27.4 d 22.4 q 22.4 q 22.6 q 28.0 q 27.9 q
7.72 s 3.05 sept 1.28 d 1.32 d 1.42 s 1.43 s 1.67 s
a J (Hz) 1: 1R,1β ) 13; 1R,2R ) 2.5; 1R,2β ) 5.5; 1β,2R ) 15; 1β,2β ) 5; 2R,2β ) 14; 2R,3R ) 3; 2R,3β ) 16; 3R,3β ) 13. b J (Hz) 4: 2R,2β ) 14.5; 2R,3R ) 2β,3β ) 3.5; 2R,3β ) 16; 3R,3β ) 15. c J (Hz) 5: 1R,1β ) 13; 1R,2R ) 1β,2R ) 3; 2R,2β ) 14.
Scheme 1. Formation of salvibretol from microstegiol
1.62) enhanced C-4 (δ 85.0) and C-18 (δ 26.3); other enhancements are in agreement with the given structure of compound 1. The HREIMS of the second compound, 1-oxosalvibretol (4), indicated a molecular formula of C20H24O3 (m/z 312.1744). The 13C-NMR spectrum (Table 1) displayed the presence of a diterpenoid structure consisting of four methyl quartets for five methyl groups, two methylene triplets, four methine doublets, and nine quarternary singlets. The 1H-NMR spectrum of 4 showed similarities to that of compound 1. The presence of an isopropyl group followed from the methyl doublets at δ 1.28 and 1.33 (each 3H, J ) 7 Hz, H-16 and H-17) and a methine septet at δ 3.35 (1H, J ) 7 Hz, H-15). Three methyl singlets were at δ 1.22 (H-18), 1.67 (H-19), and 2.32 (H20). Other signals were at δ 3.04 (1H, ddd, J ) 3.5, 15.0, 16.0 Hz, H-3β), 5.96 (C-4 OH, D2O exchangeable), 7.11 (1H, d, J ) 8.5 Hz, H-6), 7.41 (1H, s, H-14), 7.62 (1H, d, J ) 8.5 Hz, H-7). When compared to compound 1, an additional oxo group was observed at δ 210.8 in the 13C-NMR spectrum of 4, which could only be placed at C-1 due to the lack of H-1β at δ 3.83, which was as confirmed by the SINEPT experiment. The HETCOR experiment showed the direct correlations between the carbons and protons (Table 1). In the SINEPT experiment, when H-3β (δ 3.04) was irradiated, C-1 (δ 210.8) was enhanced; when H-3R (δ 2.67) was irradiated C-1 (δ 210.8), C-2 (δ 35.1), and C-4 (δ 84.3) were enhanced; irradiation of Me-19 (δ 1.67) enhanced C-4 (δ 84.3) and C-18 (δ 25.9), and irradiation of Me-18 (δ 1.22) enhanced C-4 and C-19 (δ 26.2). Irradiation of H-15 (δ 3.35) enhanced C-12 (δ 202.3) and C-14 (δ 121.1), and irradiation of H-14 (δ 7.41) enhanced C-8 (δ 126.8), C-10
(δ 147.4), C-12 (δ 202.3), and C-15 (δ 27.8). The rest of the signals are in agreement with the structure given for 4. The EIMS of 6-hydroxysalvinolone (5) indicated a molecular formula C20H26O4 (m/z 330), and the HRCIMS (m/z 331.1906) confirmed this information. The 13CNMR spectrum of 5 displayed the presence of four methyl quartets for five methyl groups, three methylene triplets, two methine doublets, and ten quarternary carbon atoms. The 1H-NMR spectrum indicated an abietane structure from signals at δ 3.05 (1H, septet, J ) 7 Hz, H-15), 1.28, and 1.32 (each 3H, d, J ) 7 Hz, H-16 and H-17) and three methyl singletssone at δ 1.67 (H-20), two others at δ 1.42 and 1.43 (H-18 and H-19)sall indicative of a double bond and a hydroxyl group at C-6 as observed in similar compounds.13 The only downfield proton was at δ 7.72 (1H, s, H-14), which suggested the presence of a carbonyl group at C-7. The signal at δ 3.00 (1H, br dd, J ) 13.0, 3.2 Hz, H-1β) indicated a hydroxyl group at C-11.14 Acetylation of 5 yielded the acetyl derivative (5a) having three acetyl signals at δ 2.37 (6H, s, 2 × OAc) and 2.32 (3H, s, OAc). After acetylation, the two methyl groups at C-4 were shifted upfield to δ 1.23 and 1.27, thus indicating that the effect of C-6 hydroxylation on the C-4 methyl groups had disappeared, while the proton signal at C-14 moved to δ 8.12 showing a more pronounced carbonyl effect on the proton at C-14. The 13C-NMR signals (Table 1) correlated with the proposed structure for compound 5. The spectral data of compound 6 were quite similar to those of taxodione,11 with the only difference being the presence of one more hydroxyl group. The HREIMS indicated a molecular formula of C20H26O4 (m/z 330.1822). The 1H-NMR spectrum displayed three methyl singlets at δ 1.32, 1.28, and 1.10, indicating the presence of three methyl groups at C-18, C-19, and C-20 and two methyl doublets at δ 0.95 and 0.85 (each 3H, d, J ) 7 Hz, H316 and H3-17), together with a methine signal at δ 2.92 (1H, d of septet, J ) 1, 7 Hz, H-15), showing the presence of an isopropyl group. Downfield signals were observed at δ 6.45 (1H, d, J ) 1.5 Hz, H-14) and 7.65 (1H, s, D2O exchangeable, C-11 OH). These two signals were typical for the C-ring of taxodione, but the signal
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Journal of Natural Products, 1996, Vol. 59, No. 8
Table 2.
a-c
13C-NMR
Data of Compounds 6 and 8
carbon
6
8
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
42.3 t 18.7 t 36.7 t 32.9 s 62.2 d 182.0 sa 142.3 sb 126.5 s 141.9 s 41.8 s 145.4 sb 183.4 sa 138.4 s 133.1 d 26.9 d 21.4 q 21.4 q 32.5 q 21.8 q 21.0 q
42.3 t 18.6 t 36.7 t 33.5 s 62.1 d 181.1 s 141.0 s 126.7 s 145.5 s 41.7 s 136.8 s 200.4 s 144.8 s 133.1 d 27.0 d 21.4 qc 21.2 qc 32.8 q 21.5 q 21.0 q
Topcu and Ulubelen
carbons, when the monomeric units were linked in compound 8, were found to be different from those in 7. The HREIMS of 8 indicated a molecular formula of C40H50O6 (m/z 626.3722). The 1H-NMR spectrum showed methyl signals at δ 1.02, 1.20, and 1.26 (each 3H, s) for H3-18, H3-19, and H3-20. Two other methyl signals were at δ 0.78 and 0.88 (each 3H, d, J ) 7 Hz, H3-16 and H3-17), and a methine doublet of septets at δ 2.96 (1H, J ) 1.2, 7 Hz, H-15) as well as a singlet at δ 2.92 (1H, s, H-5) were also observed. Downfield signals were observed at δ 6.37 (1H, d, J ) 1.2 Hz, H-14) and 7.18 (1H, s, D2O exchangeable, C-7 OH), which was quite similar to compound 6. All 1H- and 13C-NMR spectral data of compound 8 indicated a symmetrical dimeric compound, with the presence of a C-7 hydroxyl group (at δH 7.18; δC 141.0) as well as a H-14 signal (δH 6.37; δC 133.1), so that the two parts of the molecule were joined together at C-11-C-11′ to form 11,11′-didehydroxy-7,7′-dihydroxytaxodione.
Exchangeable assignments.
Experimental Section at δ 5.77 (H-7) present in taxodione was not observed in compound 6, and instead there was a signal at δ 7.22 (1H, s, D2O exchangeable) consistent with the presence of a second hydroxyl group at C-7. Because there was no proton geminal to the second hydroxyl group, it could not be placed at C-1-C-3, which exhibited three aliphatic methylene triplets in the 13C-NMR spectrum (Table 2). The only possible carbons for the second hydroxyl group were either at C-7 or C-14. Because the proton at δ 6.45 is a doublet that coupled with H-15 from spin-decoupling experiments, the second hydroxyl group was placed at C-7. The appearance of a singlet signal at δ 2.90 (H-5) was also indicative of a taxodione structure. The 13C-NMR spectrum of 6 displayed four methyl quartets for five methyl groups, three methylene triplets, three methine doublets, and nine quarternary carbon singlets (Table 2). The given data indicated that compound 6 is 7-hydroxytaxodione. The HREIMS of compound 7 showed a molecular formula of C40H50O6 (m/z 626.3720). The 1H NMR spectrum of 7 resembled those of taxodione and 7-hydroxytaxodione, with methyl singlets at δ 1.41, 1.24, and 1.05, corresponding to H3-18, H3-19, and H3-20; two methyl doublets at δ 1.08 and 1.10 (each 3H, d, J ) 7 Hz, H-16 and H-17); and a methine proton at δ 2.98 (1H, d septet, J ) 1.2, 7 Hz, H-15); H-5 was at δ 2.71, occurring as a sharp singlet. There were only two downfield signals at δ 6.60 (1H, d, J ) 1.2 Hz, H-14) and 7.63 (1H, s, C-11 OH, D2O exchangeable). The presence of a fragment peak at m/z 313 in its mass spectrum assignable to half of the structure indicated that the compound could be a dimeric taxodione. In case of a symmetrical dimer the linkages of two taxodione molecules could be either at C-14, C-11, C-7 or, if the compound is asymmetric, the conjunction could be between C-7-C-14, C-11-C-7, or C-11-C-14. In the 1HNMR spectrum of 7, the signals indicated a symmetrical dimer, otherwise more signals should have been observed for the olefinic protons. In the 1H-NMR spectrum, the H-11 and H-14 signals were clearly seen as in taxodione, so the only plausible place for two units to join together was C-7-C-7′. The spectral data indicated that compound 7 is 7,7′-bistaxodione. The final new compound, 8, was also dimeric, and its spectral data were quite similar to those of 7. Only the
General Experimental Procedures. The spectra were recorded with the following instruments: IR, Perkin-Elmer 983; UV, Varian-Techtron 635; 1H and 13C NMR, Bruker AC 200L; SINEPT experiments were recorded on a Bruker 300 MHz instrument; HRMS, VG ZabSpec. Plant Material. The roots of S. montbretii were collected from southeastern Turkey (Gu¨reniz-Nizip, Gaziantep) in July 1993. A voucher specimen is deposited in the Herbarium of Faculty of Pharmacy, University of Ankara, AEF 17915. Extraction and Isolation. The dried and roughly powdered roots of the plant (1.7 kg) were extracted with Me2CO at room temperature. After evaporation of the solvent, 42 g of a residue were obtained and fractioned on a Si gel column (5 × 70 cm) eluting with petroleum ether, followed by a gradient of CH2Cl2 up to 100%, and finally by MeOH. The following compounds were isolated in succession: microstegiol (2) (25 mg), salvibretol (1) (25 mg), saprorthoquinone (12 mg), salvinolone (27 mg), 6-hydroxysalvinolone (5) (20 mg), 1-oxosalvibretol (4) (15 mg), 1-oxoaethiopinone (8 mg), taxodione (150 mg), ferruginol (15 mg), 7-hydroxytaxodione (6) (17 mg), candidissiol (3) (20 mg), 11-hydroxy-12-methoxy-8,11,13-abietatriene (24 mg), 7,7′-bistaxodione (7) (12 mg), 11,11′-didehydroxy-7,7′-dihydroxytaxodione (8) (18 mg), salvicanaric acid (12 mg), limbinol (8 mg), and salvilimbinol (7 mg). Salvibretol (1): [R]20D +7° (c 0.1, CHCl3); UV (MeOH) λ max (log ) 335 (3.1), 303 (3.7), 290 (3.8), 240 (4.2) nm; IR (CHCl3) ν max 3450, 3100, 2980, 2920, 2870, 1700, 1620, 1600, 1565, 1500, 1450, 1420, 1370, 1320, 1210, 1170, 1080, 1000, 940 cm-1; 1H- and 13C-NMR data (CDCl3, 300 and 75.4 MHz) see Table 1; HRCIMS m/z [M + 1]+ 299.1988 C20H27O2 (calcd 299.2010); EIMS (70 eV) m/z [M]+ 298 (65), [M - 15]+ 283 (15), 243 (30), 229 (100), 201 (18), 185 (15), 97 (18), 83 (24), 69 (37). 1-Oxosalvibretol (4): [R]22D +15.2° (c 0.1, CHCl3); UV (MeOH) λ (log ) 336 (3.0), 305 (3.7), 290 (3.7), 245 (4.2) nm; IR (CHCl3) ν max 3450, 3050, 2980, 2860, 1720, 1705, 1610, 1600, 1570, 1510, 1450, 1370, 1210, 1160, 1120, 1090, 1000, 980 cm-1; 1H- and 13C-NMR data (CDCl3, 300 and 75.4 MHz) see Table 1; HREIMS m/z [M]+ 312.1744 C20H24O3 (calcd 312.1725); EIMS (70
Abietane Diterpenes from Salvia
eV); m/z [M]+ 312 (40), [M - 15]+ 297 (10), 243 (100), 224 (25), 152 (10), 128 (18), 108 (13), 69 (5). 6-Hydroxysalvinolone (5): [R]22D +42° (c 0.1, CHCl3); UV (MeOH) λ (log ) 345 (3.0), 287 (3.8), 245 (sh), 210 (4.7) nm; IR (CHCl3) ν max 3400, 3050, 2960, 2920, 2880, 1690, 1660, 1600, 1560, 1460, 1370, 1320, 1210, 1140, 1060, 1000, 750 cm-1; 1H- and 13C-NMR data (CDCl3, 200 and 50.32 MHz) see Table 1; HRCIMS m/z [M + 1]+ 331.1906 C20H27O4 (calcd 331.1909); EIMS (70 eV) m/z [M]+ 330 (100), [M - Me]+ 315 (80), 300 (15), 285 (8), 261 (10), 218 (7), 83 (15), 69 (9), 57 (20). 6-Hydroxysalvinolone acetate (5a): IR (CHCl3) ν max 2970, 1725 and 1735, 1680, 1650, 1595, 1560, 1460, 1370, 1310, 1255, 1145, 1060, 995, 765 cm-1; 1H NMR (CDCl3, 200 MHz) δ 1.28 and 1.30 (each 3H, d, J ) 7.1 Hz, H3-16 and H3-17), 1.23 and 1.27 (each 3H, s, H3-18 and H3-19), 1.65 (3H, s, H3-20), 2.32 (3H, s, OAc), 2.37 (6H, s, 2 × OAc), 2.98 (1H, dd, J ) 12.6, 3.0 Hz, H-1β), 8.12 (1H, s, H-14). 7-Hydroxytaxodione (6): [R]22D +42° (c 0.1, CHCl3); UV (MeOH) λ (log ) 460 (sh), 350 (sh), 316 (3.7) nm; IR (CHCl3) ν max 3400 (OH), 3050, 2980, 2820, 1695, 1640, 1630, 1460, 1365, 1300, 1250, 1150, 1060 cm-1; 1H NMR (CDCl3, 200 MHz) see text; 13C NMR (CDCl3, 50.32 MHz) see Table 2; HREIMS m/z [M]+ 330.1822 C20H26O4 (calcd 330.1830); EIMS (70 eV) m/z [M]+ 330 (12), [M 15]+ 315 (10), [M - 18]+ 312 (8), 284 (15), 256 (20), 213 (12), 166 (15), 105 (35), 82 (40), 78 (100). 7,7′-Bistaxodione (7): UV (MeOH) λ (log ) 460 (sh), 360 (sh), 318 (3.8) nm; IR (CHCl3) ν max 3560 (sh), 3430, 2960, 2920, 2880, 1710, 1685, 1610, 1460, 1420, 1370, 1300, 1230, 1050, 980, 900, 810, 760 cm-1; 1H-NMR (CDCl3, 200 MHz) see text; 13C NMR (CDCl3, 50.32 MHz) see Table 2; HREIMS m/z [M]+ C40H50O6 626.3720 (calcd 626.3727); EIMS (70 eV) m/z [M]+ 626 (100), [M - 15]+ 611 (15), [M - 28]+ 598 (20), 583 (15), 555 (10), [M/2]+ 313 (15), 285 (20), 245 (13), 217 (13), 123 (22), 109 (32), 83 (42), 59 (73). 11,11′-Didehydro-7,7′-dihydroxytaxodione (8): UV (MeOH) λ (log ) 460 (sh), 380 (sh), 320 (3.8) nm; IR
Journal of Natural Products, 1996, Vol. 59, No. 8 737
(CHCl3) ν max 3360, 2960, 2920, 2870, 1715, 1680, 1620, 1460, 1420, 1375, 1300, 1230, 1150, 900, 820, 760 cm-1; 1H NMR (CDCl , 200 MHz) see text; 13C NMR (CDCl , 3 3 50.32 MHz) see Table 2; HREIMS m/z [M]+ C40H50O6 626.3722 (calcd 626.3727); EIMS (70 eV) m/z [M]+ (100), [M - 15]+ 611 (15), [M - 28]+ 598 (20), 583 (25), 555 (12), [M/2]+ 313 (20), 243 (30), 109 (18), 83 (60), 58 (23). Acknowledgment. The authors thank Dr. S. W. Pelletier, University of Georgia, Athens, Georgia, for the SINEPT experiments of compounds 1 and 4 and also Dr. Murat Kartal, University of Ankara, for the collection and identification of the plant. One of us (A. U.) thanks the University of Istanbul Research Fund for the partial support of this study (O ¨ -7). References and Notes (1) Ulubelen, A.; Topcu, G. J. Nat. Prod. 1992, 55, 441-444. (2) Gill, R. R.; Cordell, G. A.; Topcu, G.; Ulubelen, A. J. Nat. Prod. 1994, 57, 181-185. (3) Ulubelen, A.; Topcu, G.; Lotter, H.; Wagner, H.; Eris¸, C. Phytochemistry 1994, 36, 413-415. (4) Ulubelen, A.; Topcu, G.; Lin, L.; Cordell, G. A. Phytochemistry 1992, 31, 2419-2421. (5) Lin, L.-Z.; Blasko, G.; Cordell, G. A. Phytochemistry 1989, 28, 177-181. (6) Ulubelen, A.; Topcu, G.; Tan, N. Tetrahedron Lett. 1992, 33, 7241-7244. (7) Ulubelen, A.; Topcu, G.; Tan, N. Phytochemistry 1992, 31, 36373638. (8) Rodriguez, B.; Fernandez-Gadea, F.; Savona, G. Phytochemistry 1984, 23, 1805-1806. (9) Gonzales, A. G.; Herrare, J. R.; Luis, J. G.; Ravelo, A. G.; Perales, A. J. Nat. Prod. 1987, 50, 341-348. (10) Topcu, G.; Eris¸, C.; Ulubelen, A. Phytochemistry 1996, 41, 11431147. (11) Kupchan, S. M.; Karim, A.; Marcks, C. J. Am. Chem. Soc. 1968, 90, 5923-5924. (12) Cambie, R. C.; Madden, R. J.; Parnell, J. C. Aust. J. Chem. 1971, 24, 217-221. (13) Burnell, R. H.; Desfossess, S.; Jean, M. J. Nat. Prod. 1993, 56, 627-628. (14) Hueso-Rodriguez, J. A.; Rodriguez, J. B.; Savona, G.; Bruno, M. Phytochemistry 1983, 22, 2005-2008.
NP9602224
